doi:10.1210/clinem/dgaa176 J Clin Endocrinol Metab, August 2020, 105(8):2595–2605 https://academic.oup.com/jcem 2595 CLINICAL RESEARCH ARTICLE Islet Amyloid in Patients With Diabetes Due to Exocrine Pancreatic Disorders, Type 2 Diabetes, and Nondiabetic Patients Sandra Ueberberg, 1, * Michael A. Nauck, 1, * Waldemar Uhl, 2 Chiara Montemurro, 1,3 Andrea Tannapfel, 4 Anne Clark, 5 and Juris J. Meier 1 1 Diabetes Division St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany; 2 Department of General and Visceral Surgery, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany; 3 David Geffen School of Medicine, University of California, Los Angeles, CA, US; 4 Institue of Pathology, Ruhr University Bochum, Bochum, Germany; and 5 Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK ORCiD number: 0000-0002-5835-8019 (J. J. Meier). Background: Amyloid deposits are a typical finding in pancreatic islets from patients with type 2 diabetes. Whether this is linked to the pathogenesis of type 2 diabetes is currently unknown. Therefore, we compared the occurrence of islet amyloid in patients with type 2 diabetes, diabetes secondary to pancreatic disorders, and nondiabetic individuals. Patients and methods: Pancreatic tissue from 15 nondiabetic patients, 22 patients with type 2 diabetes, and 11 patients with diabetes due to exocrine pancreatic disorders (chronic pancreatitis, pancreatic carcinoma) were stained for insulin, amyloid, and apoptosis. β-cell area, amyloid deposits, and β-cell apoptosis were quantified by morphometric analysis. Results: The proportion of islets containing amyloid deposits was significantly higher in both type 2 diabetes and diabetes due to exocrine pancreatic disorders than in healthy subjects. Islets with both amyloid and apoptosis were observed more frequently in type 2 diabetes and significantly more so in diabetes due to exocrine pancreatic disorders. In both diabetic groups, apoptotic ß-cells were found significantly more frequently in islets with more prominent amyloid deposits. Conclusions: The occurrence of amyloid deposits in both type 2 diabetes and diabetes secondary to exocrine pancreatic disorders suggests that islet amyloid formation is a common feature of diabetes mellitus of different etiologies and may be associated with a loss of pancreatic ß-cells. (J Clin Endocrinol Metab 105: 2595–2605, 2020) Key Words: amyloid, islet amyloid polypeptide, type 2 diabetes, secondary diabetes, chronic pancreatitis, pancreatic cancer Introduction Amyloid deposits are a histological hallmark of type 2 dia- betes (1-4). The main component of amyloid is human islet amyloid polypeptide (hIAPP) (5) or amylin (6), a secretory product of ß-cells, which is released in parallel with insulin (7, 8). hIAPP is secreted in a monomeric form and has a propensity for forming oligomers and, subsequently, in- soluble fibrils (9), of which the amyloid deposits are com- posed (1-4). The exact circumstances leading to amyloid deposits in certain individuals are still largely obscure. A number of previous studies have demonstrated that islet amyloid occurs more frequently in islets from *These authors contributed equally. ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals. permissions@oup.com Received 20 December 2019. Accepted 8 April 2020. First Published Online 9 April 2020. Corrected and Typeset 18 June 2020. Downloaded from https://academic.oup.com/jcem/article/105/8/2595/5818378 by guest on 14 November 2023